Process for cross-coupling aromatic boronic acids with aromatic halogen compounds or perfluoroalkylsulfonates

ABSTRACT

A process for preparing polycyclic aromatic compounds by cross-coupling aromatic boronic acids with aromatic halogen compounds or perfluoroalkylsulfonates in the presence of metallic palladium, if desired applied to a support material, as catalyst, wherein the coupling is carried out in the presence of a ligand and a base. The process of the invention allows the yield of polycyclic aromatic compounds to be significantly increased in comparison with processes not using a ligand and thus allows a yield optimum for the Pd(0)-catalyzed cross-coupling of aromatic boronic acids with aromatic halogen compounds to be achieved.

The invention relates to a process for preparing polycyclic aromaticcompounds by cross-coupling aromatic boronic acids with aromatic halogencompounds or perfluoroalkylsulfonates catalyzed by metallic palladium,if desired applied to a support material.

The palladium-catalyzed cross-coupling reaction of terminal alkynes andorganometallic alkyl, alkenyl, allyl or aryl compounds with alkyl,alkenyl, allyl or aryl halides or sulfonates has been utilized to anincreasing extent in many areas of organic synthesis for some years(see, for example B. M. Trost, T. R. Verhoeven in: ComprehensiveOrganometallic Chemistry Volume 8, p. 779 ff., Pergamon Press, Oxford 19. . . ).

The cross-coupling of metallated aryls with aromatic halides has beencarried out, for example, using Grignard and organolithium reagents(see, for example, J.-F. Fauvarque and A. Jutard, Bull. Chim. Soc. Fr.,1976, 765, A. Sekiya and N. Ishikawa, J. Organomet. Chem., 1976, 118,349, A. Sekija and N. Ishikawa, J. Organomet. Chem., 1977, 125, 281, M.Yamamura, I. Moritani and S. I. Murahashi, J. Organomet. Chem., 1975,91, C39, S. I. Murahashi, M. Yamamura, K. Yanagiswa, N. Mira and K.Kondo, J. Org. Chem., 1979, 44, 2408, A. Minato, K. Tamao, T. Hayashi,K. Suzuki and M. Kumada, Tetrahedron Lett., 1980, 845.), organozincreagents (for example, E. Negishi et al. J. Org. Chem. 42 (1977) 1822. )and organotin reagents (for example, M. Kosogi et al., Chem. Lett. 1977,301.).

Aromatic boron compounds too, such as boronic acids and theirderivatives or boranes, have already been used for coupling witharomatic halogen compounds or perfluoroalkylsulfonates (see, forexample, B. N. Miyaura, T. Yanagi, A. Suzuki in Synthetic Communications11 (1981), p. 513 ff.; M. J. Sharp, W. Cheng, V. Snieckus in TetrahedronLetters 28 (1987), p. 5093 ff.; G. W. Gray in J. Chem. Soc. Perkin TransII, 1989, p. 2041 ff. and Mol. Cryst, Sig. Cryst, 172 (1989), p. 165ff., 204 (1991), p. 43 ff and p. 91 ff.; EP 0 449 015; WO 89/12039; WO89/03821; EP 0 354 434).

All these processes are homogeneously catalyzed processes using Pd(0)complexes, in particular tetrakis(triphenylphosphine)palladium(0).

However, the disadvantage of these processes is clearly in the highcatalyst costs which make difficult the economical transfer of theprocesses to a larger production scale (kg, t). The homogeneous reactionprocedure furthermore makes difficult an efficient regeneration of thepalladium catalyst and can easily lead to contamination of the wasteformed in the reaction with palladium.

For this reason, processes have been developed which circumvent theseproblems by heterogeneous use of the catalyst. EP-A-0 152 450 describesthe coupling of Grignard reagents under heterogeneous Pd(0) catalysis.However, owing to the high reactivity of the organomagnesium component,the selection of starting materials for this process is severelylimited. The German Patent 3 930 663 describes a process for preparingliquid-crystalline compounds in which halides and organometalliccompounds, including boronic acids, are reacted in inert solvents usingmetallic palladium, if desired applied to a support material, ascatalyst, if desired in the presence of a metal alkoxide. Although thisprocedure can substantially reduce the catalyst costs and the palladiumcan easily be regenerated after the reactions are complete, this processoften gives the desired coupling product in only unsatisfactory yields.

It is therefore an object of the present invention to find a process forcoupling aromatic boronic acids with aromatic halogen compounds orperfluoroalkylsulfonates, which process does not have the disadvantagesdescribed for the previous processes.

It has surprisingly been found that in the reaction of aromatic boronicacids with aromatic halogen compounds or perfluoroalkylsulfonates in thepresence of a base and catalytic amounts of metallic palladium, ifdesired applied to a support material, excellent yields of polycyclicaromatic compounds can be obtained by addition of catalytic amounts of aligand.

The invention accordingly provides a process for preparing polycyclicaromatic compounds by cross-coupling aromatic boronic acids witharomatic halogen compounds or perfluoroalkylsulfonates in the presenceof metallic palladium, if desired applied to a support material, ascatalyst, wherein the coupling is carried out in the presence of aligand and a base.

The coupling reaction proceeds chemoselectively, so that evenelectrophilic groups such as esters or nitriles do not impair the courseof the reaction.

The catalyst system used in this process, comprising metallic palladium,if desired applied to a support material, and a ligand, is derived fromcomponents which are commercially available at low cost and which alloweconomical operation of the process. In addition, the palladium metalobtained as a solid after the reaction is complete can be easilyseparated off, regenerated and recycled to the catalyst process, whichachieves an additional lowering of the process costs and avoidscontamination of the waste products by palladium.

The addition according to the invention of catalytic amounts of a ligandallows the yield of polycyclic aromatic compounds to be significantlyincreased in comparison with processes not using a ligand and thusallows a yield optimum for the Pd(0)-catalyzed cross-coupling ofaromatic boronic acids with aromatic halogen compounds to be achieved.

To carry out the process of the invention, the aromatic boronic acid,the aromatic halogen compound or the perfluoroalkylsulfonate, the base,the catalytic amount of metallic palladium, if desired applied to asupport material, and the catalytic amount of a ligand are preferablyadded to an inert solvent or inert solvent mixture and stirred at atemperature of from 0° C. to 200° C., preferably at from 30° C. to 170°C., particularly preferably at from 50° C. to 150° C., most particularlypreferably at from 60° to 120° C., for a period of from 1 hour to 100hours, preferably from 5 hours to 70 hours, particularly preferably from10 hours to 50 hours, most particularly preferably from 15 hours to 30hours. After the reaction is complete, the Pd catalyst obtained as solidis separated off by filtration, the crude product is freed of thesolvent or the solvents and is subsequently purified by methods known tothose skilled in the art and matched to the respective product, e.g. byrecrystallization, distillation, sublimation, zone melting, meltcrystallization or chromatography.

Solvents suitable for the process of the invention are, for example,ethers, e.g. diethyl ether, dimethoxymethane, diethylene glycol dimethylether, tetrahydrofuran, dioxane, diisopropyl ether, tert-butyl methylether, hydrocarbons, e.g. hexane, iso-hexane, heptane, cyclohexane,benzene, toluene, xylene, alcohols, e.g. methanol, ethanol, 1-propanol,2-propanol, ethylene glycol, 1-butanol, 2-butanol, tert-butanol,ketones, e.g. acetone, ethyl methyl ketone, iso-butyl methyl ketone,amides, e.g. dimethylformamide, dimethylacetamide, N-methylpyrrolidone,nitriles, e.g. acetonitrile, propionitrile, butyronitrile, water andmixtures of the same.

Preferred solvents are ethers such as dimethoxyethane, diethylene glycoldimethyl ether, tetrahydrofuran, dioxane, diisopropyl ether,hydrocarbons such as hexane, heptane, cyclohexane, benzene, toluene,xylene, alcohols such as methanol, ethanol, 1-propanol, 2-propanol,1-butanol, 2-butanol, ethylene glycol, ketones such as ethyl methylketone, iso-butyl methyl ketone, amides such as dimethylformamide,dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoramide, waterand mixtures of the same.

Particularly preferred solvents are ethers, e.g. dimethoxyethane,tetrahydrofuran, hydrocarbons, e.g. cyclohexane, benzene, toluene,xylene, alcohols, e.g. ethanol, 1-propanol, 2-propanol, water andmixtures of the same.

Most particularly preferred are dimethoxyethane, benzene, toluene,ethanol, water and mixtures of the same.

Bases which are preferably used in the process of the invention arealkali metal and alkaline earth metal hydroxides, alkali metal andalkaline earth metal carbonates, alkali metal hydrogen carbonates,alkali metal and alkaline earth metal acetates, alkali metal andalkaline earth metal alkoxides, and also primary, secondary and tertiaryamines.

Particularly preferred are alkali metal and alkaline earth metalhydroxides, alkali metal and alkaline earth metal carbonates and alkalimetal hydrogen carbonates. Most particularly preferred are alkali metalhydroxides, alkali metal carbonates and alkali metal hydrogencarbonates, such as lithium carbonate, sodium carbonate, potassiumcarbonate.

The base is preferably used in the process of the invention in aproportion of from 100 to 1000 mol %, particularly preferably from 100to 500 mol %, very particularly preferably from 150 to 400 mol %, inparticular from 180 to 250 mol %, based on the aromatic boronic acid.

The catalyst used is metallic palladium, preferably palladium inpowdered form or on a support material, e.g. palladium on activatedcarbon, palladium on aluminum oxide, palladium on barium carbonate,palladium on barium sulfate, palladium on aluminum silicates such asmontmorillonite, palladium on SiO₂ and palladium on calcium carbonate,in each case having a palladium content of from 0.5 to 10% by weight,particularly preferably palladium in powdered form and also palladium onactivated carbon, palladium on barium and calcium carbonate, andpalladium on barium sulfate, in each case having a palladium content offrom 0.5 to 10% by weight, in particular palladium on activated carbonhaving a palladium content of 10% by weight.

It is also possible to use catalysts which contain further dopants, e.g.lead (Lindlar catalyst), in addition to palladium and the supportingmaterial.

The metallic palladium catalyst is used in the process of the inventionin a proportion of from 0.1 to 10 mol %, preferably from 0.2 to 5 mol %,particularly preferably from 0.5 to 3 mol %, most particularlypreferably from 0.5 to 1.5 mol %, based on the aromatic halogen compoundor the perfluoroalkylsulfonate.

Suitable ligands for the process of the invention are, for example,phosphines such as trialkylphosphines, tricycloalkylphosphines,triarylphosphines, where the three substituents on the phosphorus can beidentical or different, chiral or achiral and where one or more of theligands can link the phosphorus groups of a plurality of phosphines andwhere a part of this linkage can also be one or more metal atoms.

Examples of phosphines which can be used for the purposes of the processof the invention are trimethylphosphine, tributylphosphine,tricyclohexylphosphine, triphenylphosphine, tritolylphosphine,tris(4-dimethylaminophenyl)phosphine, bis(diphenylphosphino)methane,1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane and1,1'-bis(diphenylphosphino)ferrocene. Further suitable ligands are, forexample, diketones, e.g. acetylacetone and octafluoroacetylacetone andtertiary amines, e.g. trimethylamine, triethylamine, tri-n-propylamineand triisopropylamine.

Preferred ligands are phosphines and diketones, particular preferencebeing given to phosphines. Very particularly preferred ligands aretriphenylphosphine, 1,2-bis(diphenylphosphino)ethane,1,3-bis(diphenylphosphino)propane and1,1'-bis(diphenylphosphino)ferrocene, in particular triphenylphosphine.The ligand is used in the process of the invention in a proportion offrom 0.1 to 20 mol %, preferably from 0.2 to 15 mol %, particularlypreferably from 0.5 to 10 mol %, most particularly preferably from 1 to6 mol %, based on the aromatic halogen compound or theperfluoroalkylsulfonate.

It is also possible, if desired, to use mixtures of two or moredifferent ligands.

One class of starting compounds for the process of the inventionconsists of aromatic boronic acids, preferably those of the formula II,

    R.sup.1 (--A.sup.1).sub.k (--M.sup.1).sub.l --A.sup.2 --B(OH).sub.2 (II)

where R¹, A¹, A², M¹, k and l are as defined below:

R¹ is benzyloxy, H, F, Cl, Br, --NC, --CN, --CF₃, --OCF₃ or astraight-chain or branched alkyl radical (with or without an asymmetriccarbon atom) having from 1 to 18 carbon atoms, where one or twononadjacent --CH₂ -- groups can also be replaced by --O--, --S--,--CO--, --CO--O--, --O--CO--, --CO--S--, --S--CO--, --O--CO--O--,--CH--CH--, --C.tbd.C--, or --Si(CH₃)₂ --, and where one or morehydrogen atoms of the alkyl radical can also be replaced by F, Cl, Br orCN,

A¹ is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl,pyridine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogen atomscan be replaced by halogen atoms, cyano and/or methyl groups,trans-1,4-cyclohexylene, where one or two nonadjacent CH₂ groups can bereplaced by --O-- or --S-- and where one or two hydrogen atoms can bereplaced by halogen atoms, cyano and/or methyl groups,(1,3,4)-thiadiazole-2,5-diyl, 1,3-thiazol-2,4-diyl,1,3-thiazol-2,5-diyl, thiophene-2,4-diyl, thiophene-2,5-diyl,piperazine-1,4-diyl, piperazine-2,5-diyl, piperidine-1,4-diyl,naphthalene-2,6-diyl, bicyclo[2.2.2]octane-1,4-diyl,1,3-dioxaborinane-2,5-diyl or trans-decalin-2,6-diyl,

A² is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl,pyridine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogen atomscan be replaced by halogen atoms, cyano and/or methyl groups,1,3,4-thiadiazole-2,5-diyl, 1,3-thiazol-2,4-diyl, 1,3-thiazol-2,5-diyl,thiophene-2,4-diyl, thiophene-2,5-diyl or naphthalene-2,6-diyl,

M¹ is --O--, --S--, --CO--, --CO--O--, --O--CO--, --CO--S--, --S--CO--,--O--CO--O--, --CH₂ --O--, --OCH₂ --, --CH₂ CH₂ --, --CH═CH--,--C.tbd.C--, --CH(CN)--CH₂ --, --CH₂ --CH(CN)--, --CH═N--, --N═CH--,--CH₂ CH₂ CH₂ --O--, --OCH₂ CH₂ CH₂ --, --CH₂ CH₂ CO--O--, --O--COCH₂CH₂ -- and

k, l are each, independently of one another, zero or one.

Preferably, R¹ is benzyloxy, H, F, Cl, --CF₃, OCF₃ or a straight-chainor branched alkyl radical (with or without an asymmetric carbon atom)having from 1 to 18 carbon atoms, where one or two nonadjacent --CH₂ --groups can also be replaced by --O--, --CO--, --CO--O--, --OCO--,--O--CO--O--, --CH═CH--, --C.tbd.C--, or --Si(CH₃)₂ --, and where one ormore hydrogen atoms of the alkyl radical can also be replaced by F, Clor CN.

Particularly preferably, R¹ is benzyloxy, H or a straight-chain orbranched alkyl radical (with or without an asymmetric carbon atom)having from 1 to 18 carbon atoms, where one or two nonadjacent --CH₂ --groups can also be replaced by --O--, --CH═CH--, --C.tbd.C--, or--Si(CH₃)₂ --.

Preferably, A¹ is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl,pyridine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogen atomscan be replaced by halogen atoms, trans-1,4-cyclohexylene where one ortwo nonadjacent --CH₂ -- groups can be replaced by --O--,(1,3,4)-thiadiazol-2,5-diyl, naphthalene-2,6-diyl orbicyclo[2.2.2]octane-1,4-diyl.

Particularly preferably, A¹ is 1,4-phenylene, 2-fluoro-1,4-phenylene,2,3-difluoro-1,4-phenylene, 2,6-difluoro-1,4-phenylene,2,5-difluoro-1,4-phenylene, and also pyridine-2,5-diyl,pyrimidine-2,5-diyl, where one or two hydrogen atoms can be replaced byfluorine, or trans-1,4-cyclohexylene.

Preferably, A² is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,5-diyl,pyridine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogen atomscan be replaced by halogen atoms, or naphthalene-2,6-diyl.

Particularly preferably, A² is 1,4-phenylene, 2-fluoro-1,4-phenylene,2,3-difluoro-1,4-phenylene, 2,6-difluoro-1,4-phenylene,2,5-difluoro-1,4-phenylene, and also pyridine-2,5-diyl where one or twohydrogen atoms can be replaced by F, or naphthalene-2,6-diyl.

Preferably, M¹ is --O--, --CO--, --CO--O--, --O--CO--, --O--CO--O--,--CH₂ --O--, --O--CH₂ --, --CH₂ --CH₂ --, --CH═CH--, --C.tbd.C--, --CH₂CH₂ CH₂ --O--, --O--CH₂ CH₂ CH₂ --, --CH₂ CH₂ CO--O-- or --O--CO--CH₂CH₂ --.

Particularly preferably, M¹ is --O--, --CH₂ --O--, --O--CH₂ --, --CH₂--CH₂ --, --CH═CH-- or --C.tbd.C--.

Most particularly preferred are the aromatic boronic acids of theformulae IIa to IIh listed below: ##STR1## where R¹ is benzyloxy, H,methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl,decyl, undecyl, dodecyl, tridecyl, tetradecyl and pentadecyl, and alsomethoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy,nonoxy, decoxy, undecoxy, dodecoxy, tridecoxy, tetradecoxy andpentadecoxy.

The aromatic boronic acids used, preferably those of th e formula II,are either known or can be prepared by known methods, as described, forexample, in Houben Weyl Methoden der Organischen Chemie, GeorgThieme-Verlag, Stuttgart, Volume 13/3a. Thus it is possible, forexample, to obtain boronic acids, preferably those of the formula II,from aromatic alkali metal and magnesium compounds by reaction withtrialkoxyboranes and subsequent hydrolysis.

The second class of starting compounds for the process of the inventionconsists of aromatic halogen compounds or aromaticperfluoroalkylsulfonates, preferably those of the formula III,

    X--A.sup.3 (--M.sup.2).sub.m (--A.sup.4).sub.n --R.sup.2   (III)

where R², A³, A⁴, M², X, m and n are as defined below.

R² ie benzyloxy, H, F, Cl, Br, --NC, --CN, --CF₃, --OCF₃ or astraight-chain or branched alkyl radical (with or without an asymmetriccarbon atom) having from 1 to 18 carbon atoms, where one or twononadjacent --CH₂ -- groups can also be replaced by --O--, --S--,--CO--, --CO--O--, --O--CO--, --CO--S--, --S--CO--, --O--CO--O--,--CH═CH--, --C.tbd.C--, or --Si(CH₃)₂ --, and where one or more hydrogenatoms of the alkyl radical can also be replaced by F, Cl, Br or CN,

A⁴ is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl,pyridine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogen atomscan be replaced by halogen atoms, cyano and/or methyl groups,trans-1,4-cyclohexylene, where one or two nonadjacent CH₂ groups can bereplaced by --O-- or --S-- and where one or two hydrogen atoms can bereplaced by halogen atoms, cyano and/or methyl groups,(1,3,4)-thiadiazole-2,5-diyl, 1,3-thiazol-2,4-diyl,1,3-thiazol-2,5-diyl, thiophene-2,4-diyl, thiophene-2,5-diyl,piperazine-1,4-diyl, piperazine-2,5-diyl, piperidine-1,4-diyl,naphthalene-2,6-diyl, bicyclo[2.2.2]octane-1,4-diyl,1,3-dioxaborinane-2,5-diyl or trans-decalin-2,6-diyl,

A³ is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl,pyridine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogen atomscan also be replaced by halogen atoms, cyano and/or methyl groups,1,3,4-thiadiazole-2,5-diyl, 1,3-thiazol-2,4-diyl, 1,3-thiazol-2,5-diyl,thiophene-2,4-diyl, thiophene-2,5-diyl or naphthalene-2,6-diyl,

M² is --O--, --S--, --CO--, --CO--O--, --O--CO--, --CO--S--, --S--CO--,--O--CO--O--, --CH₂ --O--, --OCH₂ --, --CH₂ CH₂ --, --CH═CH--,--C.tbd.C--, --CH(CN)--CH₂ --, --CH₂ --CH(CN)--, --CH═N--, --N═CH--,--CH₂ CH₂ CH₂ --O--, --OCH₂ CH₂ CH₂ --, --CH₂ CH₂ CO--O--, --O--COCH₂CH₂ -- and

m, n are each, independently of one another, zero or one.

Preferably, R² is benzyloxy, H, F, Cl, Br, --CN, --CF₃, OCF₃ or astraight-chain or branched alkyl radical (with or without an asymmetriccarbon atom) having from 1 to 18 carbon atoms, where one or twononadjacent --CH₂ -- groups can also be replaced by --O--, --CO--,--CO--O--, --O--CO--, --O--CO--O--, --CH═CH--, --C.tbd.C--, or--Si(CH₃)₂ --, and where one or more hydrogen atoms of the alkyl radicalcan also be replaced by F, Cl or CN.

Particularly preferably, R² is benzyloxy, H, Cl, Br or a straight-chainor branched alkyl radical (with or without an asymmetric carbon atom)having from 1 to 18 carbon atoms, where one or two nonadjacent --CH₂ --groups can also be replaced by --O--, --CO--, --CO--O--, --O--,--O--CO--, --O--CO--O--, --CH═CH--, --C.tbd.C--, or --Si(CH₃)--.

Preferably, A³ is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl,pyridine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogen atomscan be replaced by halogen atoms, 1,3,4-thiadiazol-2,5-diyl ornaphthalene-2,6-diyl.

Particularly preferably, A³ is 1,4-phenylene, 2-fluoro-1,4-phenylene,2,3-difluoro-1,4-phenylene, 2,6-difluoro-1,4-phenylene,2,5-difluoro-1,4-phenylene, and also pyrazine-2,5-diyl,pyridazine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogenatoms can be replaced by halogen atoms or naphthalene-2,6-diyl.

Preferably, A⁴ is 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl,pyridine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogen atomscan be replaced by halogen atoms, trans-1,4-cyclohexylene, where one ortwo nonadjacent CH₂ groups can be replaced by --O--,(1,3,4)-thiadiazole-2,5-diyl, naphthalene-2,6-diyl orbicyclo[2.2.2]octane-1,4-diyl.

Particularly preferably, A⁴ is 1,4-phenylene, 2-fluoro-1,4-phenylene,2,3-difluoro-1,4-phenylene, 2,6-difluoro-1,4-phenylene,2,5-difluoro-1,4-phenylene, and also pyridine-2,5-diyl,pyrimidine-2,5-diyl, where one or two hydrogen atoms can be replaced byF, or trans-1,4-cyclohexylene.

Preferably, M² is --O--, --CO--, --CO--O--, --O--CO--, --O--CO--O--,--CH₂ --O--, --O--CH₂ --, --CH₂ --CH₂ --, --CH═CH--, --C.tbd.C--, --CH₂CH₂ CH₂ --O--, --O--CH₂ CH₂ CH₂ --, --CH₂ CH₂ CO--O-- or --O--CO--CH₂CH₂ --.

Particularly preferably, M² is --O--, --CO--, --CO--O--, --O--CO--,--O--CO--O--, --CH₂ --O--, --O--CH₂ --, --CH₂ --CH₂ --, --CH--CH--,--C.tbd.C--, --CH₂ CH₂ CH₂ --O--, --O--CH₂ CH₂ CH₂ --, --CH₂ CH₂ CO--O--or --O--CO--CH₂ CH₂.

Preferably, X is chlorine, bromine or OSO₂ --C_(p) F_(2p+1), where p isan integer from 1 to 10. Particularly preferably, X is chlorine orbromine.

Most particularly preferred are the aromatic halogen compounds of theformula III 1 to III 24 shown below, ##STR2## where R² is benzyloxy, H,methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl,decyl, undecyl, dodecyl, tridecyl, tetradecyl and pentadecyl, and alsomethoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy,nonoxy, decoxy, undecoxy, dodecoxy, tridecoxy, tetradecoxy andpentadecoxy.

The aromatic halogen compounds and perfluoroalkylsulfonates preferablythose of the general formula III, are either known or can be prepared byknown methods, as are described, for example, in Houben Weyl, Methodender Organischen Chemie, Georg Thieme-Verlag, Stuttgart, Volume 5/3 and5/4. For example, the aromatic halides can be obtained by replacing thediazonium group in a corresponding diazonium salt by chlorine, bromineor iodine.

Furthermore, hydroxy-substituted nitrogen heterocycles can be convertedby means of phosphorus trihalides and phosphorus oxytrihalides into thecorresponding halides. The process of the invention for cross-couplingaromatic boronic acids with aromatic halogen compounds orperfluoroalkylsulfonates can likewise be used for preparing compounds ofthe formula III. Perfluoroalkylsulfonates of the formula III, where X isOSO₂ --C_(n) H_(2n+1), can be prepared by esterification ofcorresponding alcohols of the formula III, where X is a hydroxyl group,with perfluoroalkanesulfonic acids or their reactive derivatives. Thecorresponding perfluoroalkanesulfonic acids are known. Suitable reactivederivatives of the said perfluoroalkanesulfonic acids are, inparticular, the acid halides, especially the chlorides and bromides,also the anhydrides.

Products of the process of the invention are polycyclic aromaticcompounds.

Preferred products of the process of the invention are compounds of theformula I,

    R.sup.1 (--A.sup.1).sub.k (--M.sup.1).sub.l --A.sup.2 --A.sup.3 (--M.sup.2).sub.m (--A.sup.4).sub.n --R.sup.2             (I)

where R¹ and R² can be, independently of one another, benzyloxy, H, F,Cl, Br, --NC, --CN, --CF₃, --OCF₃ or a straight-chain or branched alkylradical (with or without an asymmetric carbon atom) having from 1 to 18carbon atoms, where one or two nonadjacent --CH₂ groups can alsoreplaced by --O--, --S--, --CO--, --CO--O--, --O--CO--, --CO--S--,--S--CO--, --O--CO--O--, --CH═CH--, --C.tbd.C--, or --Si(CH₃)₂ --, andwhere one or more hydrogen atoms of the alkyl radical can also bereplaced by F, Cl, Br or CN,

A¹ and A⁴ can each be, independently of one another, 1,4-phenylene,pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl,pyrimidine-2,5-diyl, where one or two hydrogen atoms can be replaced byhalogen atoms, cyano and/or methyl groups, trans-1,4-cyclohexylene whereone or two nonadjacent CH₂ groups can be replaced by --O-- or --S-- andwhere one or two hydrogen atoms can be replaced by halogen atoms, cyanoand/or methyl groups, (1,3,4)-thiadiazole-2,5-diyl,1,3-thiadiazole-2,4-diyl, 1,3-thiazole-2,5-diyl, thiophene-2,4-diyl,thiophene-2,5-diyl, piperazine-1,4-diyl, piperazine-2,5-diyl,piperidine-1,4-diyl, naphthalene-2,6-diyl,bicyclo[2.2.2]octane-1,4-diyl, 1,3-dioxaborinane-2,5-diyl ortrans-decalin-2,6-diyl,

A² and A³ can each be, independently of one another, 1,4-phenylene,pyrazine-2,5-diyl, pyridazine-3,6-diyl, pyridine-2,5-diyl,pyrimidine-2,5-diyl, where one or two hydrogen atoms can be replaced byhalogen atoms, cyano and/or methyl groups, 1,3,4-thiadiazole-2,5-diyl,1,3-thiazole-2,4-diyl, 1,3-thiazole-2,5-diyl, thiophene-2,4-diyl,thiophene-2,5-diyl or naphthalene-2,6-diyl,

M¹ and M² can each be, independently of one another, --O--, --S--,--CO--, --CO--O--, --O--CO--, --CO--S, --S--CO--, --O--CO--O--, --CH₂--O--, --OCH₂ --, --CH₂ CH₂ --, --CH═CH--, --C.tbd.C--, --CH(CN)--CH₂--, --CH₂ --CH(CN)--, --CH≡N--, --N═CH--, --CH₂ CH₂ CH₂ --O--, --OCH₂CH₂ CH₂ --, --CH₂ CH₂ CO--O--, --O--COCH₂ CH₂ --,

and

k, l, m, n are each, independently of one another, zero or one.

Preferred and particularly preferred variants of R¹, R², A¹, A², A³, A⁴,M¹, M², k, l, m, n are specified in the formulae II and III.

Most particularly preferred are the compounds of the formula I 1 to I 94shown below ##STR3## where R¹ and R² are benzyloxy, H, methyl, ethyl,propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl,dodecyl, tridecyl, tetradecyl and pentadecyl, and also methoxy, ethoxy,propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, nonoxy, decoxy,undecoxy, dodecoxy, tridecoxy, tetradecoxy and pentadecoxy.

The compounds of the formula I are suitable for use asliquid-crystalline materials, or can be used as intermediates for thepreparation of further liquid-crystalline compounds. Furthermore,compounds of the formula I are also suitable as precursors forpharmaceuticals, cosmetics, fungicides, herbicides, insecticides, dyes,detergents and polymers, including additives for the same.

The present invention is illustrated by the Examples described below,without however being limited, where the abbreviations used have thefollowing meanings:

mp.=melting point

X=crystalline

S=smectic

S_(C) =smectic C

S_(A) =smectic A

N=nematic

I=isotropic

EXAMPLE 1 5-Bromo-2-[4-(phenylmethoxy)phenyl]pyrimidine

104.25 g (0.438 mol) of 2,5-dibromopyrimidine, 100.00 g (0.438 mol) of4-(phenylmethoxy)benzeneboronic acid, 4.75 g (0.00438 mol) of palladium(10%) on activated carbon, 4.50 g (0.01752 mol) of triphenylphosphineand 93.00 g (0.876 mol) of sodium carbonate are heated in 1000 ml oftoluene, 500 ml of ethanol and 300 ml of water for 24 hours at 80° C.The palladium catalyst is subsequently separated off from the reactionmixture at 80° C. by filtration. The aqueous lower phase of the reactionmixture is separated off at 80° C., before the organic phase is freed ofthe solvents on a rotary evaporator and dried in a high vacuum. Thecrude product thus obtained is recrystallized from acetonitrile (3000ml), giving 150.07 g (97% yield, based on 2,5-dibromopyridine) of5-bromo-2-[4-(phenylmethoxy)phenyl]pyrimidine (purity according to HPLC:98%). ##STR4## mp.: 153°-155° C.

COMPARATIVE EXAMPLE 1 Synthesis of5-bromo-2-[4-(phenylmethoxy)phenyl]pyrimidine by the process describedin DE 39 30 663

4.17 g (17.54 mmol) of 2,5-dibromopyrimidine, 4.00 g (17.54 mmol) of4-(phenylmethoxy)benzeneboronic acid, 0.19 g (0,175 mmol) of palladium(10%) on activated carbon and 3.72 g (35.10 mmol) of sodium carbonateare reacted in 42 ml of toluene, 21 ml of ethanol and 12.5 ml of waterusing a similar method to Example 1.

Analysis (HPLC) of the crude product indicates a mixture which containsthe starting materials 2,5-dibromopyrimidine,4-(phenylmethoxy)benzeneboronic acid and unidentified products inaddition to 6.3% of the desired product5-bromo-2-[4-(phenylmethoxy)phenyl]pyrimidine.

      - Example No. R.sup.1 A.sup.1 A.sup.2 A.sup.3 A.sup.4 R.sup.2 Yield     Phase transitions      2 H.sub.17 C.sub.8      O     ##STR5##      ##STR6##       Br 97%     3      ##STR7##      ##STR8##      ##STR9##       Br 99%     4 H.sub.17 C.sub.8      O     ##STR10##      ##STR11##       Br 96%     5 H      ##STR12##      ##STR13##       Br 93%     6 H.sub.13      C.sub.6     ##STR14##      ##STR15##      ##STR16##      H 98 X 97 S.sub.A 133 I     7 H.sub.13 C.sub.6      O     ##STR17##      ##STR18##      ##STR19##      H 95% X 92 S.sub.A 163 I     8 H.sub.13      C.sub.6     ##STR20##      ##STR21##      ##STR22##      O(CH.sub.2).sub.4 CHCH2 90% X 70 S.sub.4 62 S.sub.3 108 S.sub.C 146     S.sub.A 189 I     9      ##STR23##      ##STR24##      ##STR25##       H 85%     10 H.sub.17 C.sub.8      O     ##STR26##      ##STR27##       H 91%     11 H.sub.17 C.sub.8      O     ##STR28##      ##STR29##       H 87%     12 H.sub.17 C.sub.8      O     ##STR30##      ##STR31##       H 81%     13 H      ##STR32##      ##STR33##      ##STR34##      O(CH.sub.2).sub.8      CHCH2 92% X 96 S.sub.A 91                       14      ##STR35##      ##STR36##      ##STR37##      ##STR38##       Br 95%     15 H.sub.17 C.sub.8      O     ##STR39##      ##STR40##      ##STR41##       H 83% X 148 S.sub.3 149 S.sub.C 150 S.sub.A 162 I     16 H.sub.17 C.sub.8      O     ##STR42##      ##STR43##      ##STR44##       H 80% X 95 S.sub.3 111 S.sub.C 116 S.sub.A 132 I     17 H.sub.7      C.sub.3     ##STR45##      ##STR46##      ##STR47##       Br 93%     18 H.sub.11      C.sub.5     ##STR48##      ##STR49##      ##STR50##       Br 89%     19 H.sub.17      C.sub.8     ##STR51##      ##STR52##      ##STR53##       Br 90%     20 H.sub.11      C.sub.5     ##STR54##      ##STR55##      ##STR56##       H 85%     21 H.sub.11      C.sub.5     ##STR57##      ##STR58##      ##STR59##       H 82%     22 H.sub.17 C.sub.8      O     ##STR60##      ##STR61##       Br 89%     23 H.sub.2      CCH(CH.sub.2).sub.8O     ##STR62##      ##STR63##       Br 93%     24 H.sub.17 C.sub.8      O     ##STR64##      ##STR65##       OC.sub.8      H.sub.17 96% X 64 S.sub.C 67 S.sub.A 91 I              25 H.sub.17 C.sub.8      O     ##STR66##      ##STR67##       O(CH.sub.2).sub.8      CHCH2 80% X 59 S.sub.C 66 S.sub.A 80 I                        26 H.sub.13 C.sub.6      O     ##STR68##      ##STR69##       O(CH.sub.2).sub.8      CHCH2 83% X 56 S.sub.A 80 I                        27 H.sub.21 C.sub.10      O     ##STR70##      ##STR71##       OC.sub.8      H.sub.17 90% X 67 S.sub.C 74 S.sub.A 89 I              28 H.sub.2      CCH(CH.sub.2).sub.8O     ##STR72##      ##STR73##       C.sub.8      H.sub.17 94% X (65) S.sub.A 64 I             29 H.sub.2      CCH(CH.sub.2).sub.8O     ##STR74##      ##STR75##      ##STR76##      H 96% X 87 S.sub.A 125 I     30 H      ##STR77##      ##STR78##       Br 82%     31 H      ##STR79##      ##STR80##      ##STR81##       OC.sub.10      H.sub.21 90% X 125 S.sub.A 154 I                32 H      ##STR82##      ##STR83##      ##STR84##       OC.sub.8      H.sub.17 92% X 133 S.sub.A 153 I              33 H      ##STR85##      ##STR86##      ##STR87##       Br 87%     34 H.sub.17 C.sub.8      O     ##STR88##      ##STR89##      ##STR90##      OC.sub.2      H.sub.5 93% X 91 S.sub.C 100 S.sub.A 218 I             35 H.sub.17 C.sub.8      O     ##STR91##      ##STR92##      ##STR93##      OC.sub.8      H.sub.17 96% X 91 S.sub.C 190 S.sub.A 194 I             36 H.sub.17 C.sub.8      O     ##STR94##      ##STR95##      ##STR96##      O(CH.sub.2).sub.9      CHCH2 87% X 83 S.sub.C 175 S.sub.A 179 I                       37 H.sub.17 C.sub.8      O     ##STR97##      ##STR98##      ##STR99##      O(CH.sub.2).sub.2      CHCH2 90% X 89 S.sub.C 159 S.sub.A 207 I                       38 H.sub.17 C.sub.8      O     ##STR100##      ##STR101##       OC.sub.8      H.sub.17 85%              39 H.sub.17 C.sub.8      O     ##STR102##      ##STR103##      ##STR104##      OC.sub.8 H.sub.17 92% X 87 S.sub.3 116 S.sub.C 158 S.sub.A 163 I                                                                       40     H.sub.13 C.sub.6      O     ##STR105##      ##STR106##      ##STR107##      OC.sub.8 H.sub.17 96% X 85 S.sub.4 93 S.sub.3 119 S.sub.C 161 S.sub.A     169 I     41 H.sub.17 C.sub.8      O     ##STR108##      ##STR109##      ##STR110##      C.sub.8      H.sub.17 99% X 62 S.sub.3 96 S.sub.C 116 S.sub.A 133 I            42 H.sub.13 C.sub.6      O     ##STR111##      ##STR112##      ##STR113##      C.sub.8 H.sub.17 96% X 44 S.sub.4 92 S.sub.3 99 S.sub.C 118 S.sub.A 138     I     43 H.sub.17 C.sub.8      O     ##STR114##      ##STR115##      ##STR116##      OC.sub.8      H.sub.17 82% X 91 S.sub.A 95 I             44 H.sub.17 C.sub.8      O     ##STR117##      ##STR118##      ##STR119##      OC.sub.8      H.sub.17 85% X 91 S.sub.C 110 S.sub.A 116 I             45 H.sub.17 C.sub.8      O     ##STR120##      ##STR121##      ##STR122##      OC.sub.8      H.sub.17 81% X 124 I             46 H.sub.17 C.sub.8      O     ##STR123##      ##STR124##      ##STR125##      OC.sub.8      H.sub.17 80% X 65 S.sub.C 85 S.sub.A 104 I             47 H.sub.17 C.sub.8      O     ##STR126##      ##STR127##      ##STR128##      OC.sub.8      H.sub.17 87% X 100 S.sub.C 127 N 128 I             48 H.sub.17 C.sub.8      O     ##STR129##      ##STR130##      ##STR131##      C.sub.5      H.sub.11 93% X 78 S.sub.A 110 N 117 I            49 H.sub.21 C.sub.10      O     ##STR132##      ##STR133##      ##STR134##      C.sub.5      H.sub.11 89% X 64 S.sub.A 108 N 112 I            50 H.sub.25 C.sub.12      O     ##STR135##      ##STR136##      ##STR137##      C.sub.5      H.sub.11 90% X 62 S.sub.A 104 N 107 I            51 H.sub.17 C.sub.8      O     ##STR138##      ##STR139##       OC.sub.8      H.sub.17 94% X 58 S.sub.A 86 I              52 H.sub.17 C.sub.8      O     ##STR140##      ##STR141##      ##STR142##       OC.sub.6      H.sub.13 86% X 105 S.sub.C 174 N 188 I              53 H.sub.17 C.sub.8      O     ##STR143##      ##STR144##      ##STR145##       OC.sub.8      H.sub.17 80% X 105 S.sub.C 176 N 182 I              54 H.sub.17 C.sub.8      O     ##STR146##      ##STR147##      ##STR148##       C.sub.7      H.sub.15 81% X 58 S.sub.2 65 S.sub.C 157 N 164 I             55 H.sub.17 C.sub.8      O     ##STR149##      ##STR150##      ##STR151##       C.sub.6      H.sub.13 83% X 55 S.sub.2 58 S.sub.C 153 N 163 I             56 H.sub.17 C.sub.8      O     ##STR152##      ##STR153##      ##STR154##       H 91%     57 H      ##STR155##      ##STR156##      ##STR157##       OC.sub.8      H.sub.17 86% X 107 (80) S.sub.A 85 N 101 I              58 H.sub.17 C.sub.8      O     ##STR158##      ##STR159##      ##STR160##      ##STR161##      C.sub.8 H.sub.17 80% X 73 S.sub.3 173 S.sub.C 273 S.sub.A 275 N 281 I     59 H.sub.17 C.sub.8      O     ##STR162##      ##STR163##       Br 97%     60 H.sub.17 C.sub.8      O     ##STR164##      ##STR165##       H 92%

We claim:
 1. A process for preparing polycyclic aromatic compounds bycross-coupling aromatic boronic acids with aromatic halogen compounds orperfluoroalkylsulfonates in the presence of metallic palladium, ifdesired applied to a support material, as catalyst, wherein the couplingis carried out in the presence of a ligand selected from the groupconsisting of phosphines, diketones and tertiary amines and a base. 2.The process as claimed in claim 1, wherein a polycyclic aromaticcompound of the formula I

    R.sup.1 (--A.sup.1).sub.k (--M.sup.1).sub.l --A.sup.2 --A.sup.3 (--M.sup.2).sub.m (--A.sup.4).sub.n --R.sup.2             (I)

where R¹ and R² can be, independently of one another, benzyloxy, H, F,Cl, Br, --NC, --CN, --CF₃, --OCF₃ or a straight-chain or branched alkylradical (with or without an asymmetric carbon atom) having from 1 to 18carbon atoms, where one or two nonadjacent --CH₂ groups can also bereplaced by --O--, --S--, --CO--, --CO--O--, --O--CO--, --CO--S--,--S--CO--, --O--CO--O--, --CH═CH--, --C.tbd.C--, or --Si(CH₃)₂ --, andwhere one or more hydrogen atoms of the alkyl radical can also bereplaced by F, Cl, Br or CN, A¹ and A⁴ can each be, independently of oneanother, 1,4-phenylene, pyrazine-2,5-diyl, pyridazine-3,6-diyl,pyridine-2,5-diyl, pyrimidine-2,5-diyl, where one or two hydrogen atomscan be replaced by halogen atoms, cyano and/or methyl groups,trans-1,4-cyclohexylene where one or two nonadjacent CH₂ groups can bereplaced by --O-- or --S-- and where one or two hydrogen atoms can bereplaced by halogen atoms, cyano and/or methyl groups,(1,3,4)-thiadiazole-2,5-diyl, 1,3-thiazole-2,4-diyl,1,3-thiazole-2,5-diyl, thiophene-2,4-diyl, thiophene-2,5-diyl,piperazine-1,4-diyl, piperazine-2,5-diyl, piperidine-1,4-diyl,naphthalene-2,6-diyl, bicyclo[2.2.2]octane-1,4-diyl,1,3-dioxaborinane-2,5-diyl or trans-decalin-2,6-diyl, A² and A³ can eachbe, independently of one another, 1,4-phenylene, pyrazine-2,5-diyl,pyridazine-3,6-diyl, pyridine-2,5-diyl, pyrimidine-2,5-diyl, where oneor two hydrogen atoms can be replaced by halogen atoms, cyano and/ormethyl groups, 1,3,4-thiadiazole-2,5-diyl, 1,3-thiazole-2,4-diyl,1,3-thiazole-2,5-diyl, thiophene-2,4-diyl, thiophene-2,5-diyl ornaphthalene-2,6-diyl, M¹ and M² can each be, independently of oneanother, --O--, --S--, --CO--, --CO--O--, --O--CO--, --CO--S--,--S--CO--, --O--CO--O--, --CH₂ --O--, --OCH₂ --, --CH₂ CH₂ --,--CH═CH--, --C.tbd.C--, --CH(CN)--CH₂ -- --CH₂ --CH(CN)--, --CH═N--,--N═CH--, --CH₂ CH₂ CH₂ --O--, --OCH₂ CH₂ CH₂ --, --CH₂ CH₂ CO--O--,--O--COCH₂ CH₂ --, k, l, m, n are each, independently of one another,zero or one, is prepared by reacting boronic acids of the formula II

    R.sup.1 (--A.sup.1).sub.k (--M.sup.1).sub.l --A.sup.2 --B(OH).sub.2 (II)

where R¹, A¹, A², M¹, k and l are as defined above, with a compound ofthe formula (III)

    X--A.sup.3 (--M.sup.2).sub.m (--A.sup.4).sub.n --R.sup.2   (III)

where R², A³, A⁴, M², m and n are as defined above, and X is chlorine,bromine, iodine or OSO₂ --C_(p) F_(2p+1), where p is an integer from 1to
 10. 3. The process as claimed in claim 1, wherein the ligand is addedin a proportion of 0.1-20 mol %, based on the aromatic halogen compoundor the aromatic perfluoroalkylsulfonate.
 4. The process as claimed inclaim 1, wherein the base used is at least one compound selected fromthe group consisting of alkali metal and alkaline earth metalhydroxides, alkali metal and alkaline earth metal carbonates, alkalimetal hydrogen carbonates, alkali metal and alkaline earth metalacetates, alkal metal and alkaline earth metal alkoxides and primary,secondary and tertiary amines.
 5. The process as claimed in claim 4,wherein the base is used in a proportion of 100-500 mol %, based on thearomatic boronic acid.
 6. The process as claimed in claim 1, carried outat temperatures between 50° and 150° C.
 7. The process as claimed inclaim 1, wherein the cross-coupling reaction is carried out in a solventor solvent mixture which contains at least one compound selected fromthe group consisting of ethers, hydrocarbons, alcohols, ketones, amides,nitriles and water.
 8. The process as claimed in claim 1, wherein thecatalyst used is palladium in powdered form, palladium on activatedcarbon, palladium on aluminum oxide, palladium on barium sulfate orpalladium on calcium carbonate, in each case having a palladium contentof from 0.5 to 10% by weight.